Abstract
Purpose:
Previous reports have described ultrastructural changes to Bruch’s membrane and/or the retinal pigment epithelium (RPE) including sub-RPE deposit formation in mice following a high fat diet. However, these mice also had an additional insult either through a genetic defect or following excessive light exposure or smoke inhalation. A “fast food” diet consisting of high fat, high cholesterol, and high fructose fed to wild-type mice revealed markedly different liver pathology with associated inflammation compared to mice fed a “standard” high fat diet. Since many retinal diseases including age-related macular degeneration are characterized by inflammation, we investigated whether the fast food diet causes changes to retinal morphology in wild type mice.
Methods:
Three-month old genetically unaltered C57Bl/6J mice were fed either standard rodent chow or a diet containing high fat, high cholesterol, and high fructose-supplemented drinking water for 8-months. Whole eyes were enucleated from the mice, fixed in 4% paraformaldehyde in 0.1M phosphate buffer, processed, sectioned and examined by transmission electron microscopy.
Results:
Mice fed a fast food diet (n=3) were 34% (p=0.04) heavier than mice fed a standard rodent chow (n=3). Compared to controls, fast food fed mice had retinal changes including attenuation, vacuolation and loss of nuclei in the RPE; thickened Bruch’s membrane; basal laminar deposits; thinning of the nerve fiber layer; and attenuation and nuclear pleomorphism of retinal ganglion cells.<br />
Conclusions:
Wild-type C57BL/6J mice fed a diet containing elevated fat, cholesterol and fructose exhibit age-related morphological changes to the inner and outer retina. This model may provide insight into the pathogenesis of age-related retinal disorders and enable the testing of new therapies.